1) Antibodies to the CDR2- and CDR3-like domain of CD4 can bind simultaneously to discrete epitopes on the CD4 molecule, and both block gpl20 binding to CD4, demonstrating separate binding sites for gpl20 within the CDR2 and CDR3-like domains of CD4. These antibodies as well as derivatized peptides from the CDR3-like domain of CD4 block infection in vitro by primary/clinical isolates of HIV-l that are resistant to blockade by soluble CD4. Both the CDR2- and CDR3-like domains of CD4 appear to be critical for HIV- I infection of CD4-positive cells. 2) Attempts to develop high-affinity anti-CDR3-directed anti-CD4 antibodies as immunotherapeutic agents using human/mouse chimeric CD4 molecules as immunogens, are in progress. Anti-idiotypic as well as direct immunoprotective strategies for blocking HIV infection in vivo will be attempted in rhesus macaque monkeys infected with SIV upon development of conjugate rhesus-specific 3) Diffuse regional cerebrocortical astrogliosis and increased expression of somatostatin mRNA in layer four of cerebral cortex have been identified in SW-infected rhesus macaques with motor and/or cognitive impairment regardless of the presence or stage of AIDS, suggesting that these are early and potentially reversible alterations caused by primate immunodeficiency virus infection within the brain, that may be linked to the motor and cognitive impairment observed. 4) Attempts to colonize murine brain with bone-marrow derived cells tagged with retroviral expression vectors have been successful, suggesting that inflammatory cells of hematopoietic origin might be genetically altered ex vivo to provide therapeutic products at otherwise inaccessible sites of inflammation in the HIV-infected central nervous system.